a Insect Infection and Immunity Lab, Department of Biological Sciences , Institute for Biomedical Sciences, The George Washington University , Washington DC , USA.
Virulence. 2017 Nov 17;8(8):1668-1682. doi: 10.1080/21505594.2017.1330240. Epub 2017 Jun 2.
Previous and recent investigations on the innate immune response of Drosophila have identified certain mechanisms that promote pathogen elimination. However, the function of Thioester-containing proteins (TEPs) in the fly still remains elusive. Recently we have shown the contribution of TEP4 in the antibacterial immune defense of Drosophila against non-pathogenic E. coli, and the pathogens Photorhabdus luminescens and P. asymbiotica. Here we studied the function of Tep genes in both humoral and cellular immunity upon E. coli and Photorhabdus infection. We found that while Tep2 is induced after Photorhabdus and E. coli infection; Tep6 is induced by P. asymbiotica only. Moreover, functional ablation of hemocytes results in significantly low transcript levels of Tep2 and Tep6 in response to Photorhabdus. We show that Tep2 and Tep6 loss-of-function mutants have prolonged survival against P. asymbiotica, Tep6 mutants survive better the infection of P. luminescens, and both tep mutants are resistant to E. coli and Photorhabdus. We also find a distinct pattern of immune signaling pathway induction in E. coli or Photorhabdus infected Tep2 and Tep6 mutants. We further show that Tep2 and Tep6 participate in the activation of hemocytes in Drosophila responding to Photorhabdus. Finally, inactivation of Tep2 or Tep6 affects phagocytosis and melanization in flies infected with Photorhabdus. Our results indicate that distinct Tep genes might be involved in different yet crucial functions in the Drosophila antibacterial immune response.
先前和近期对果蝇固有免疫反应的研究已经确定了某些促进病原体清除的机制。然而，TEP（硫酯蛋白）在果蝇中的功能仍然难以捉摸。最近我们已经表明，TEP4 在果蝇对非致病性大肠杆菌、病原菌 Photorhabdus luminescens 和 P. asymbiotica 的抗菌免疫防御中具有重要作用。在这里，我们研究了 Tep 基因在大肠杆菌和 Photorhabdus 感染后对体液和细胞免疫的功能。我们发现，TEp2 在 Photorhabdus 和大肠杆菌感染后被诱导，而 Tep6 仅被 P. asymbiotica 诱导。此外，血淋巴细胞的功能缺失导致对 Photorhabdus 的 Tep2 和 Tep6 转录水平显著降低。我们表明，Tep2 和 Tep6 功能丧失突变体对 P. asymbiotica 的存活时间延长，Tep6 突变体对 P. luminescens 的感染存活更好，而两个 tep 突变体对大肠杆菌和 Photorhabdus 都具有抗性。我们还发现，在感染大肠杆菌或 Photorhabdus 的 Tep2 和 Tep6 突变体中，免疫信号通路的诱导存在明显的模式。我们进一步表明，Tep2 和 Tep6 参与了果蝇对 Photorhabdus 反应中血淋巴细胞的激活。最后，Tep2 或 Tep6 的失活会影响感染 Photorhabdus 的果蝇的吞噬作用和黑化作用。我们的结果表明，不同的 Tep 基因可能参与了果蝇抗菌免疫反应中的不同但关键的功能。
